The present invention relates to a series of new derivatives of M-4 and IsoM-4, to processes for preparing them and to pharmaceutical compositions containing them.
M-4 and IsoM-4, which are described in U.S. patent application Ser. No. 270,846, filed Jun. 5, 1981, to A. Terahara and M. Tanaka which issued as U.S. Pat. No. 4,346,227, when in the form of their lactones, have the formulae: ##STR2## respectively. The formulae given above show the compounds in their lactone form; of course, under appropriate conditions, the lactone can be hydrated to give the corresponding hydroxy-carboxylic acid.
M-4 and IsoM-4 are amongst a number of compounds which may be derived from the group of compounds collectively designated ML-236 and described, for example, in U.S. Pat. No. 3,983,140. Other compounds having a similar structure and collectively designated MB-530 have been discovered and are described, for example, in United Kingdom patent specifications No. 2,046,737, No. 2,049,664 and No. 2,055,100, and derivatives of both the ML-236 and MB-530 compounds are described, for example, in United Kingdom patent specification No. 2,075,013. Of the many compounds there are known which have structures of the ML-236 or MB-530 type, most have shown some ability to inhibit the biosynthesis of cholesterol and some have shown this ability to a sufficient degree that they might be of value in the treatment of such disorders as hyperlipaemia (especially hypercholesteraemia) and arteriosclerosis.
We have now discovered a series of compounds which are derivatives of M-4 and IsoM-4 and which, whilst retaining the ability of their parent compound to inhibit the biosynthesis of cholesterol, are far less readily deactivated in vivo than are the parent compounds.